OBJECTIVES: To examine associations between sleep and alcohol, amphetamine, cigarette, marijuana, and non-heroin narcotic use among US middle and high school students, trends in associations over time, and the comparative impact of select covariates on association strength. METHODS: Data from the 1991-2014 nationally representative Monitoring the Future study of 8(th)-, 10(th)-, and 12(th)-grade US students were used to estimate standardized correlations between the frequency of getting at least 7 hours of sleep (7+ sleep) and substance use frequency while simultaneously regressing both outcomes on key covariate domains. RESULTS: As 7+ sleep frequency increased, substance use frequency significantly decreased and vice versa. Overall, association strength was inversely associated with grade. Associations were generally modest, varied across substances, and weakened over the historical period examined for 8(th)- and 10(th)- graders. Associations showed little variance by sex and racial/ethnic subgroups. Controlling for deviance, psychosocial and general health covariates significantly attenuated association strength. CONCLUSIONS: Among US secondary students, 7+ sleep/substance use associations were largely explained by individual deviance, psychosocial, and general health characteristics. Awareness and exploitation of these shared associations may be useful in improving substance use prevention and/or treatment efforts.